Flaugh, U.S. Pat. No. 4,576,959, discloses a family of 6-substituted-4-dialkylamino-1,3,4,5-tetrahydrobenz[cd]indoles, described as central serotonin agonists and useful as anti-depressants. Flaugh discloses 6-bromo-1,2,2a,3,4,5-hexahydrobenz[cd]indoles as intermediates to certain of the disclosed compounds, in particular the 6-aminocarbonyl containing compounds. In the process disclosed by Flaugh, the bromo substituent is displaced with cyano by reaction with cuprous cyanide, and the cyano group is subsequently hydrolyzed to provide the aminocarbonyl substituent.
A method has been reported for preparing primary or secondary amides by reacting aryl, heterocyclic or vinylic halides with carbon monoxide and a primary or secondary amine in the presence of a palladium catalyst. (A. Schoenberg and R. F. Heck, J. Org. Chem., 39, p. 3327, 1974) It has also been reported that esters can be formed using an alcohol in place of the amine in the catalyzed reaction. (A. Schoenberg, I. Bartoletti, and R. F. Heck, J. Org. Chem., 39, p 3318, 1974) These references teach that aryl bromides and aryl iodides are both useful substrates for this palladium catalyzed carbonylation reaction.
We have discovered that while the 6-bromo-1,2,2a,3,4,5-hexahydrobenz[cd]indoles of Flaugh are unsuitable as substrates for this carbonylation reaction, the palladium-catalyzed reaction of 6-iodo-1,2,2a,3,4,5-hexahydrobenz[cd]indoles with carbon monoxide and ammonia is surprisingly facile, proceeding rapidly and in high yield to provide 6-aminocarbonyl-1,2,2a,3,4,5-hexahydrobenz[cd]indoles which can be converted to 6-aminocarbonyl-1,2,3,4-tetrahydrobenz[cd]indoles. It has also been found that alkyl and aryl substituted amides and esters in the 6-position can be prepared using amines or alcohols respectively with the 6-iodo-1,2,2a,3,4,5-hexahydrobenz[cd]indoles.